PROJECT SUMMARY In response to RFA-DA-17-014, HIV, HCV and Related Comorbidities in Rural Communities Affected by Opioid Injection Drug Epidemics in the United States: Building Systems for Prevention, Treatment and Control (UG3/UH3), we propose a multi-phase, mixed-methods study that aims to implement and evaluate a novel community response model, which we have named the Community-Based, Client-Centered Prevention Home. Using the organizational infrastructure of a large, multi-site syringe service program serving a geographically disperse population of people who inject drugs in rural communities across Northern Wisconsin, we will build locally responsive systems to facilitate uptake of evidence-based prevention services for high-risk clients. The Client-Centered Prevention Home model incorporates prevention case management and mobile health information technology into traditional harm-reduction services delivered at syringe service programs, which we hypothesize will increase use prevention services. During the UG3 phase, we will perform needs assessments in 6 rural Wisconsin counties in partnership with local stakeholders, and use respondent driven sampling to conduct a cross-sectional epidemiologic evaluation to estimate the prevalence of HIV, viral hepatitis and sexually transmitted infections. Contingent upon meeting recruitment and data collection goals, in the UH3 phase of the project we will deploy and evaluate the Client-Centered Prevention Home model in the 3 counties demonstrating highest vulnerability to worsening epidemics of opioid injection. The 3 remaining counties not selected for implementation will serve as comparison sites in a quantitative evaluation of program effectiveness during year 5. The growing problem of opioid injection in rural Wisconsin is highly significant because it exemplifies trends observed nationally indicating severe vulnerability to worsening epidemics of HIV, HCV, and opioid overdose deaths in rural communities that are substantially underserved by evidence-based prevention interventions. This proposal is highly innovative because it will be the first study to use an evidence-based mHealth strategy and a formal implementation science approach to enhance coordination of prevention services in syringe service programs. It has potential for high impact because of our team's state-wide reach, broad access to at-risk individuals, and robust infrastructure for conducting a rigorous, multi-site evaluation of our proposed model.